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β 2 ‐Adrenoreceptors Stimulate c‐ fos Transcription Through Multiple Cyclic AMP‐ and Ca 2+ ‐Responsive Elements in Cerebellar Granular Neurons
Author(s) -
Barthel F.,
Loeffler J. Ph.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64010041.x
Subject(s) - ap 1 transcription factor , second messenger system , cyclic amp response element binding protein , transcription (linguistics) , transcription factor , creb , protein kinase a , cerebellum , biology , microbiology and biotechnology , messenger rna , transcriptional regulation , protein kinase c , c fos , signal transduction , kinase , gene expression , gene , endocrinology , genetics , linguistics , philosophy
Neurons from the granular layer of the cerebellum express functional β 2 ‐adrenoreceptors (β 2 ‐ARs). We show that stimulation of β 2 ‐ARs with isoprenaline increases cyclic AMP (cAMP) production and stimulates transcription of genes containing the cAMP‐responsive element (CRE; TGACGTCA). This effect is mediated by cAMP‐dependent protein kinase and the trans ‐acting factor CRE binding protein. Transcriptional regulation by the β 2 ‐AR was investigated by using the c‐ fos protooncogene as a model system. We show that β 2 ‐ARs stimulate c‐ fos mRNA accumulation, increase AP 1 binding activity, and stimulate transcription through the phorbol ester‐responsive element (TGACTCA). The transcriptional regulation of c‐ fos itself was studied with reporter constructs driven by c‐ fos promoter sequences. Deletion studies revealed that β 2 ‐ARs stimulate c‐ fos transcription through at least three distinct regulatory sequences: (a) the CRE located at −60 bp 5′ to the initiation site, (b) the fos AP 1 ‐like element (−291 to −297), and (c) the serum‐responsive element (−297 to −317). The regulation of these elements by the two putative second messengers of the β 2 ‐AR, cAMP and Ca 2+ , was analyzed. We report that all three of these regulatory sequences are coregulated by both second messengers. These results indicate that β 2 ‐ARs stimulate c‐ fos transcription by multiple cAMP‐ and Ca 2+ ‐dependent regulatory elements in neurons.